Video games are ubiquitous, can improve health behavior, but have not been evaluated as a tool to promote protection from HIV transmission in minority early adolescents. A major challenge in HIV prevention for minority adolescents is capturing individuals in their environment - meeting individuals where they live. The current application combines proven HIV prevention strategies and an interactive video game platform that incorporates virtual environments and intelligent conversant virtual characters to address this challenge. Research demonstrates that adolescents who acquire new knowledge, skills and attitudes in a video game, and practice these skills in the game, are more likely to behave similarly in real life. Therefore, the goal of this application is to adapt existing software to develop and refine an interactive video game designed to decrease HIV risk by teaching minority adolescents sex, drug and alcohol negotiation and refusal skills. The game will be adapted with input from minority adolescents, and collaborators with expertise in positive youth development, social cognitive theory and self-efficacy, prospect theory and message framing, software and artificial intelligence development, and commercial game design. We will evaluate the efficacy of the game by conducting a randomized clinical trial in 330 minority youths, ages 9-14 years, attending an after-school and/or weekend youth program, who will be randomly assigned to play the interactive HIV prevention video game, Retro-Warriors, or to play a commercial off-the-shelf video game. Subjects will play two sessions/week of their assigned game for four weeks. The primary outcome will be initiation of sexual activity, defined as the initiation of either vaginal or anal intercourse. Secondary outcomes include HIV risk behavior knowledge, social competency, self-efficacy, drug/alcohol use behaviors and overall risk-taking behaviors. We hypothesize that the experimental group will have lower rates of initiation of sexual activity and have higher knowledge scores at 1, 6, 12, and 24 months compared with the control group. We will also explore if selected baseline characteristics are associated with an improved response to the negotiation skills training intervention embedded in the interactive video game. Unique features of this intervention will include the use of virtual characters or avatars who can verbally respond to and interact with the player, a realistic virtual urban setting, the use of sex, drug/alcohol risk challenges that the subjects can practice repeatedly, the use of message framing according to prospect theory, a fun and engaging intervention that encourages repeated involvement, and the ability to track the players' choices and behaviors in the game. The successful implementation of this application will represent a paradigm shift, providing evidence for the role of interactive games as HIV/AIDS prevention in minority adolescents. Video game technology has the potential to expand the available vehicles for HIV prevention to the increasing number of electronic gaming platforms including the internet, personal digital assistants, and cell phones, thereby creating a new avenue for public health interventions. PUBLIC HEALTH RELEVANCE: This research is designed to develop and test a video game that will teach minority adolescents how to avoid sex, drug and alcohol risk behaviors that can lead to HIV infection. The research goes beyond the use of a game for education and proposes to create an interactive world in which the game players can engage in role-playing to learn to avoid risky behaviors. This application has far-reaching implications including the potential for this technology to travel with the player, i.e., the player ultimately can do sessions from home, on a console, a cell phone, or a personal digital assistant. There are international implications given that access to the internet is growing in developing countries and these technologies could be transferred to adolescents in countries experiencing a growing HIV epidemic but who have limited access to targeted risk reduction strategies. If successful, the results of this research will be video game technology that can improve individual and public health and decrease HIV transmission.